Romano-Ward syndrome (RWS) is purely a cardiac electrophysiologic disorder, characterized by QT prolongation and T-wave abnormalities on the ECG and the ventricular tachycardia torsade de pointes (TdP). TdP is usually self-terminating, thus causing a syncopal event, the most common symptom in individuals with RWS. Syncope typically occurs during exercise and high emotions, less frequently at rest or during sleep, and usually without warning. In some instances, TdP degenerates to ventricular fibrillation and causes aborted cardiac arrest (if the individual is defibrillated) or sudden death. Approximately 50% of individuals with a disease-causing mutation in one of the genes associated with RWS have symptoms, usually one to a few syncopal spells. While cardiac events may occur from infancy through middle age, they are most common from the pre-teen years through the 20s.
Diagnosis of RWS is established by prolongation of the QTc interval in the absence of specific conditions known to lengthen it (for example, QT-prolonging drugs) and/or molecular genetic testing of the genes known to be associated with RWS, of which KCNQ1 (locus name LQT1), KCNH2 (locus name LQT2) and SCN5A (locus name LQT3) are the most common. Other, less frequently involved genes are KCNE1 (locus name LQT5), KCNE2 (locus name LQT6), CAV3 (locus name LQT9), SCN4B (locus name LQT10), AKAP9 (locus name LQT11), SNTA1 (locus name LQT12) and KCNJ5 (locus name LQT13). Approximately 25% of families meeting clinical diagnostic criteria for RWS do not have detectable mutations in one of the above genes.
RWS is inherited in an autosomal dominant manner. Most individuals diagnosed with RWS have an affected parent. The proportion of cases caused by de novo mutations is small. Each child of an individual with RWS has a 50% risk of inheriting the disease-causing mutation. Penetrance of the disease may vary. Prenatal testing for pregnancies at increased risk in families in which the disease-causing mutation is known is available.